GDC-0941

GDC-0941 is an inhibitor of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). It inhibits class I catalytic subunits of PI3K p110α, β, δ, and γ with IC₅₀ values of 3, 33, 3, and 75 nM, respectively, by binding near the ATP binding pocket (Folkes et al.; Berndt et al.). It shows selectivity against class II, III, and IV PI3K isoforms as well, but with lower efficacy; for example, it inhibits phosphatidylinositol-4-phosphate 3-kinase C2 domain subunit β (C2β, Class II) and mammalian target of rapamycin (mTOR, Class IV) in the high nanomolar range and most others in the micromolar range (Folkes et al.).

CANCER RESEARCH

• Inhibits proliferation of multiple cancer cell lines, such as U87MG (glioblastoma), PC3 (prostate) and MDA-MB-361 (breast) lines, in vitro and in mouse xenograft models (Folkes et al.; Raynaud et al.; O'Brien et al.).
• Induces apoptosis and inhibits xenograft tumor growth in combination with a MAP/ERK kinase (MEK) inhibitor GDC-0973 (Hoeflich et al.).